2-keto-D-gluconic acid can be prepared from D-glucose by fermentation, usually several subsequent fermentation steps are required. According to U.S. Pat. No. 4,879,229, U.S. Pat. No. 5,134,077, U.S. Pat. No. 5,234,819 and DE 42 38 905, D-glucose is fermented to 2,5-diketo-gluconic acid by micro-organisms of the genus Erwinia. According to U.S. Pat. No. 843,946 the obtained product is reduced by sodium hydride to a mixture of 2-keto-D-gluconic acid and 2-keto-L-gulonic acid. U.S. Pat. No. 4,180,511 describes a method to further improve the above-mentioned reduction. The main disadvantage of this process is the use of sodium hydride to perform the reduction, thus demanding heavily controlled reaction procedures. Moreover, the final products; 2-keto-L-gulonic acid and 2-keto-D-gluconic acid are obtained in quasi-equimolar amounts, thereby bringing the reaction efficiency to a theoretical maximum of about 50%.
U.S. Pat. No. 3,282,795 and D. Bull (Biotechnology and Bioengineering Vol. XXIII (1981) 373-389) describe the direct fermentative conversion of D-glucose into 2-keto-D-gluconic acid by Serratia marcescens, giving conversion rates as high as 95-100%. However, these conventional fermentation processes have disadvantages in that the volume of the fermentor is large and that the production costs are rather high.
EP 0 042 221 and J. Geigert (Carb. Res 113, (1983) 163-165) describe the enzymatic oxidation of D-glucose to D-glucosone by pyranose-2-oxidase followed by an enzymatic oxidation by D-glucose-1-oxidase to convert D-glucosone into 2-keto-D-gluconic acid. Although the conversion of D-glucosone into 2-keto-D-gluconic acid is nearly quantitative, the overall process is producing 2 moles of hydrogen peroxide per mole of 2-keto-D-gluconic acid. This excess of hydrogen peroxide has to be destroyed by catalase to avoid destruction of the enzyme and degradation of the reaction product This co-processing requires a lot of efforts and is adding up to processing costs.
Chemical oxidation of D-gluconic acid derivatives to 2-keto-D-gluconic acid gives, according to U.S. Pat. No. 2,153,311 low yields (40%) in the presence of chromic acid and iron sulphate as co-catalyst. Long reaction times (12 hours to 3 days) and high amounts of salts are the major drawbacks of this method.
According to U.S. Pat. No. 4,620,034 and EP 0 151 498, it is possible to apply catalytic oxidation to obtain 2-keto-D-gluconic acid from D-glucose or D-gluconic acid. Molecular oxygen is applied in the presence of a platinum-based catalyst, which is doped with lead or bismuth. Within 7-10 minutes 73 and 87% of 2-keto-D-gluconic acid, starting from D-glucose and D-gluconic acid, respectively are obtained. However, a slight increase in the reaction time (a few minutes) results in a dramatic drop of the yield of 2-keto-D-gluconic acid. It is not mentioned how to avoid this rapid degradation while at the same time maintaining the high yields of 2-keto-D-gluconic acid. It is not indicated what type of working-up procedure is to be used in order to avoid the degradation of 2-keto-D-gluconic acid into mainly oxalic acid. Moreover, the reaction time is very short and the required settings are too critical to set-up a reasonable large-scale process, since under the claimed reaction condition the product is very sensitive to degradation. Finally, the pH of the reaction medium is kept constant at pH=8 by the addition of alkali, preferably in the form of sodium hydroxide or a carbonate.
NL 9302127 describes the conversion of an aldonic acid to a 2-keto-aldonic acid which is also disclosed in EP 0 151 498. It indicates that the pH during the oxidation should be between 3 and 6.9 and that in a preferred embodiment the pH is not regulated and thus allowed to drop during the course of the reaction. 2-keto-D-gluconic acid, has a variety of commercial uses. In the form of the calcium salt, it is used in photography, mainly in developer formulations. It can also readily be converted into other commercially useful products such as furfural, D-arabinose, D-ribulose, and iso-ascorbic acid.
There exists a need for an economically feasible chemical process which gives high yields of 2-keto-D-gluconic acid within a reasonable reaction time and which maintains the amount of 2-keto-D-gluconic acid constant at high level and yet, has all the advantages of the catalytic oxidation process. The reaction time should be such that on an industrial scale the reaction can be worked-up within a reasonable time-frame without having the disadvantages of loosing high amounts of the desired product. The present invention provides such a method.